Multimorbidity, healthcare use and catastrophic health expenditure by households in India: a cross-section analysis of self-reported morbidity from national sample survey data 2017-18.

BACKGROUND: The purpose of this research is to generate new evidence on the economic consequences of multimorbidity on households in terms of out-of-pocket (OOP) expenditures and their implications for catastrophic OOP expenditure. METHODS: We analyzed Social Consumption Health data from National Sample Survey Organization (NSSO) 75th round conducted in the year 2017-2018 in India. The sample included 1,13,823 households (64,552 rural and 49,271 urban) through a multistage stratified random sampling process. Prevalence of multimorbidity and related OOP expenditure were estimated. Using Coarsened Exact Matching (CEM) we estimated the mean OOP expenditure for individuals reporting multimorbidity and single morbidity for each episode of outpatient visits and hospital admission. We also estimated implications in terms of catastrophic OOP expenditure for households. RESULTS: Results suggest that outpatient OOP expenditure is invariably lower in the presence of multimorbidity as compared with single conditions of the selected Non-Communicable Diseases(NCDs) (overall, INR 720 [USD 11.3] for multimorbidity vs. INR 880 [USD 14.8] for single). In the case of hospitalization, the OOP expenditures were mostly higher for the same NCD conditions in the presence of multimorbidity as compared with single conditions, except for cancers and cardiovascular diseases. For cancers and cardiovascular, OOP expenditures in the presence of multimorbidity were lower by 39% and 14% respectively). Furthermore, around 46.7% (46.674-46.676) households reported incurring catastrophic spending (10% threshold) because of any NCD in the standalone disease scenario which rose to 63.3% (63.359-63.361) under the multimorbidity scenario. The catastrophic implications of cancer among individual diseases was the highest. CONCLUSIONS: Multimorbidity leads to high and catastrophic OOP payments by households and treatment of high expenditure diseases like cancers and cardiovascular are under-financed by households in the presence of competing multimorbidity conditions. Multimorbidity should be considered as an integrated treatment strategy under the existing financial risk protection measures (Ayushman Bharat) to reduce the burden of household OOP expenditure at the country level.

Hybrid CT-angiography (Angio-CT) for combined CT and fluoroscopic procedures in interventional radiology enhances utilization.

PURPOSE: To investigate the utilization of an angiography-CT (Angio-CT) system and its advantages for single patient encounters. METHODS: Interventions utilizing both CT and fluoroscopy to perform multiple procedures in a single encounter or single interventions using both were identified. Cases were stratified by complexity (defined by RVUs). Comparative analyses of room (TRoom) and total encounter (TEncounter) times were performed between non-complex bundled cases and controls. RESULTS: Between June 2018 and August 2019, 1108 procedures were performed via the Angio-CT system; 10% (114/1108) used both fluoroscopy and CT. 21% (24/114) Involved more than one procedure in a single encounter that required a CT-only and fluoroscopy-only bundled procedure. 59% (67/114) were non-complex, and 70% (80/114) were non-oncologic. 82.5% (14/17) of non-complex bundled procedures demonstrated TRoom below the mean of their respective controls; 52.8% (9/17) were 2 standard deviations below the control means. Pleural catheter placement following post-lung biopsy pneumothorax was the most common non-complex bundled case with a significant reduction in TRoom when performed via Angio-CT compared to control (99 vs. 163 min, p < 0.0001). There was a significant reduction in TEncounter for abdominopelvic drain placement procedures bundled with either (1) percutaneous nephrostomy tube evaluation with or without replacement, or (2) central venous catheter placement (211 min vs. 344 min, p < 0.001 and 231 min vs. 347 min, p < 0.05, respectively). CONCLUSION: The primary use for the hybrid Angio-CT system was to perform non-oncologic and non-complex cases with potential reduction in TRoom and TEncounter for specific non-complex bundled cases.

CHCHD4 (MIA40) and the mitochondrial disulfide relay system.

Mitochondria are pivotal for normal cellular physiology, as they perform a crucial role in diverse cellular functions and processes, including respiration and the regulation of bioenergetic and biosynthetic pathways, as well as regulating cellular signalling and transcriptional networks. In this way, mitochondria are central to the cell's homeostatic machinery, and as such mitochondrial dysfunction underlies the pathology of a diverse range of diseases including mitochondrial disease and cancer. Mitochondrial import pathways and targeting mechanisms provide the means to transport into mitochondria the hundreds of nuclear-encoded mitochondrial proteins that are critical for the organelle's many functions. One such import pathway is the highly evolutionarily conserved disulfide relay system (DRS) within the mitochondrial intermembrane space (IMS), whereby proteins undergo a form of oxidation-dependent protein import. A central component of the DRS is the oxidoreductase coiled-coil-helix-coiled-coil-helix (CHCH) domain-containing protein 4 (CHCHD4, also known as MIA40), the human homologue of yeast Mia40. Here, we summarise the recent advances made to our understanding of the role of CHCHD4 and the DRS in physiology and disease, with a specific focus on the emerging importance of CHCHD4 in regulating the cellular response to low oxygen (hypoxia) and metabolism in cancer.

Quality of life assessment & out-of-pocket expenditure in multiple myeloma: An observational study.

Background & objectives: Prognosis of patients with multiple myeloma (MM) has improved significantly in the past two decades. However, the symptoms burden is high at onset and treatment is generally prolonged with significant financial burden. This study was undertaken to assess the quality of life (QoL) and to analyse out-of-pocket expenditure (OOPE) incurred on MM patients being treated at a tertiary care cancer centre in north India. Methods: This observational, cross-sectional study included 116 patients (aged >18 yr) of MM (both newly diagnosed and those with recurrent disease). For QoL assessment, European Organisation for Research and Treatment of Cancer (EORTC)-validated questionnaire (EORTC QLQ C 30 version 3.0) and disease-specific QLQ MY20 were used. For assessing OOPE incurred on treatment, the National Sample Survey Organisation (NSSO) questionnaire was used. Results: Bone pains (68.1%), fatigue (59.7%) and dyspnoea (54.6%) were common symptoms. The mean global health status/QoL score was 59.62±19.21. International Staging System (ISS) score correlated with global health status score, and gastritis was the main adverse effect. QoL score showed negative correlation to side effects of treatment (-0.53) of MY20 domain. On multivariate analysis, ISS stage (P<0.001) and adverse effects of treatment (P=0.02) were predictive factors. The median OOPE was ₹ 7900 (IQR, ₹ 4950-13,550) towards medical and ₹ 1150 (IQR, ₹ 500-3100) for non-medical expenses for the past one month. Interpretation & conclusions: Regular assessment of QoL in the clinical management of multiple myeloma patients has the potential of improving treatment outcomes. Measures to reduce out-of-pocket expenditure may improve treatment compliance.

Old drugs, new uses: Drug repurposing in hematological malignancies.

Discovery and development of novel anti-cancer drugs are expensive and time consuming. Systems biology approaches have revealed that a drug being developed for a non-cancer indication can hit other targets as well, which play critical roles in cancer progression. Since drugs for non-cancer indications would have already gone through the preclinical and partial or full clinical development, repurposing such drugs for hematological malignancies would cost much less, and drastically reduce the development time, which is evident in case of thalidomide. Here, we have reviewed some of the drugs for their potential to repurpose for treating the hematological malignancies. We have also enlisted resources that can be helpful in drug repurposing.

CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain.

Background: Tumour cells rely on glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) to survive. Thus, mitochondrial OXPHOS has become an increasingly attractive area for therapeutic exploitation in cancer. However, mitochondria are required for intracellular oxygenation and normal physiological processes, and it remains unclear which mitochondrial molecular mechanisms might provide therapeutic benefit. Previously, we discovered that coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (CHCHD4) is critical for regulating intracellular oxygenation and required for the cellular response to hypoxia (low oxygenation) in tumour cells through molecular mechanisms that we do not yet fully understand. Overexpression of CHCHD4 in human cancers correlates with increased tumour progression and poor patient survival. Results: Here, we show that elevated CHCHD4 expression provides a proliferative and metabolic advantage to tumour cells in normoxia and hypoxia. Using stable isotope labelling with amino acids in cell culture (SILAC) and analysis of the whole mitochondrial proteome, we show that CHCHD4 dynamically affects the expression of a broad range of mitochondrial respiratory chain subunits from complex I-V, including multiple subunits of complex I (CI) required for complex assembly that are essential for cell survival. We found that loss of CHCHD4 protects tumour cells from respiratory chain inhibition at CI, while elevated CHCHD4 expression in tumour cells leads to significantly increased sensitivity to CI inhibition, in part through the production of mitochondrial reactive oxygen species (ROS). Conclusions: Our study highlights an important role for CHCHD4 in regulating tumour cell metabolism and reveals that CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain and CI biology.

Quantifying the financial burden of households' out-of-pocket payments on medicines in India: a repeated cross-sectional analysis of National Sample Survey data, 1994-2014.

OBJECTIVE: The objective of this research is to generate new evidence on financial implications of medicines out-of-pocket (OOP) payments for households. Another objective is to investigate which disease conditions contributed to a significant proportion of households' financial burden. SETTING: All Indian states including union territories, 1993-2014. DESIGN: Repeated cross-sectional household surveys. DATA: Secondary data of nationwide Consumer Expenditure Surveys for the years 1993-1994, 2004-2005 and 2011-2012 and one wave of Social Consumption: Health for the year 2014 from National Sample Survey Organisation. OUTCOME MEASURES: OOP expenditure on healthcare in general and medicines in specific. RESULTS: Total OOP payments and medicines OOP payments were estimated to be 6.77% (95% CI 6.70% to 6.84%) and 4.49% (95% CI 4.45% to 4.54%) of total consumption expenditure, respectively, in the year 2011-2012 which marked significant increase since 1993-1994. These proportions were 11.46% (95% CI 11.36% to 11.56%) and 7.60% (95% CI 7.54% to 7.67%) of non-food expenditure, respectively, in the same year. Total OOP payments and medicines OOP payments were catastrophic for 17.9% (95% CI 17.7% to 18.2%) and 11.2% (95% CI 11.0% to 11.4%) households, respectively, in 2011-2012 at the 10% of total consumption expenditure threshold, implying 29 million households incurred catastrophic OOP payments in the year 2011-2012. Further, medicines OOP payments pushed 3.09% (95% CI 2.99% to 3.20%), implying 38 million persons into poverty in the year 2011-2012. Among the leading cause of diseases that caused significant OOP payments are cancers, injuries, cardiovascular diseases, genitourinary conditions and mental disorders. CONCLUSIONS: Purchase of medicines constitutes the single largest component of the total OOP payments by households. Hence, strengthening government intervention in providing medicines free in public healthcare facilities has the potential to considerably reduce medicine-related spending and total OOP payments of households and reduction in OOP-induced poverty.

Cervical cancer control in India: taking evidence to action.

The most prevalent types of human papillomavirus in cervical cancer in India are HPV 16 and HPV 18, found in 60.7 per cent and 16 per cent of cases respectively. A comprehensive strategy with a judicious mix of interventions on health promotion, specific protection (vaccination), early diagnosis (screening), and treatment should be instituted to prevent and control cervical cancer in India. Proponents of vaccination and screening argue for enhanced investments on these interventions based on their relative cost-effectiveness. For policymakers, the major concerns about these interventions remain affordability and cost to government. Herein we try to review comprehensively the evidence on prevention and control interventions and to recommend appropriate policies to guide public health decision-making.